Flare levels after intravitreal injection of brolucizumab for diabetic macular edema.

PURPOSE: This study aimed to evaluate anterior flare intensity (AFI) after intravitreal injection of brolucizumab (IVBr) in patients with diabetic macular edema (DME), and to identify the factors associated with the change of AFI after IVBr. METHODS: This prospective multicenter study was conducted at five sites in Japan for patients with DME who underwent a single IVBr. AFI and central retinal thickness (CRT) were measured using a laser flare meter and spectral-domain optical coherence tomography, respectively, at weeks 0 and 6. RESULTS: Sixty-five patients (phakia, 37 eyes; pseudophakia, 28 eyes) were enrolled. Six weeks after IVBr, CRT and best-corrected visual acuity significantly improved (p < 0.0001). AFI (p = 0.0003) and age (p = 0.0054) were significantly higher in patients with pseudophakic eyes than those with phakic eyes. The AFI of the phakic eyes decreased after IVBr (p = 0.043). As the AFI before injection is higher (p = 0.0363) and the age is lower (p = 0.0016), the AFI decreases after IVBr. There was a significant positive correlation between the rates of change in CRT and AFI (p = 0.024). CONCLUSION: After IVBr, AFI decreases in phakic eyes but not in pseudophakic eyes. The age, AFI and CRT before injection and changes of CRT are involved in the change in AFI after IVBr.

Regional Variety of Reduction in Retinal Thickness of Diabetic Macular Edema after Anti-VEGF Treatment.

Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis.

Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty.

Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

Characteristic distribution of microaneurysms and capillary dropouts in diabetic macular edema.

PURPOSE: To investigate the distribution pattern of microaneurysms (MAs) and capillary dropouts (CDOs) related to retinal thickness in patients with diabetic macular edema (DME). METHODS: We designed a cross-sectional observational study in which we manually merged fluorescein angiography and optical coherence tomography (OCT) map and located MAs and CDOs areas. The density of MAs, the width and the length of circumference of CDOs, and the number of MAs adjacent to CDOs were compared between highly thickened (white area (WA) in OCT map) and border areas (red area (RA)). RESULTS: We examined 115 eyes of 115 patients with DME. The density of MAs in RA (1.086 ± 0.616) was significantly higher than that in WA (0.8601 ± 1.086) (p = 0.002). The MA rates adjacent to CDOs in WA and RA were 79.1% and 80.7%, respectively. In the RA, the size of CDO adjacent to MAs was smaller (p = 0.013), but its circumference was longer (p = 0.018), and the number of MAs adjacent to CDOs was larger than those in WA (p = 0.002). The total length of circumference of CDOs was significantly correlated with the number of MAs adjacent to CDOs in WA (p = 0.011, R2 = 0.68) and RA (p = 0.008, R2 = 0.81). CONCLUSION: Smaller but more CDOs with longer circumference adjacent to MAs contribute to the higher density of MAs in the surrounding areas of DME.

Flare levels after intravitreal injection of ranibizumab, aflibercept, or triamcinolone acetonide for diabetic macular edema.

PURPOSE: To evaluate anterior flare intensity (AFI) and central retinal thickness (CRT) values after intravitreal injection of aflibercept (IVA), ranibizumab (IVR), or triamcinolone acetonide (IVTA) in patients with diabetic macular edema (DME). METHODS: This research was conducted as a prospective study for patients with DME. Patients with phakia received either IVA or IVR, whereas patients with pseudophakia received IVA, IVR, or IVTA. AFI and CRT were measured using a laser flare meter and spectral domain optical coherence tomography, respectively, at days 0, 1, 7, 30, and 90. RESULTS: Forty patients with phakia and 60 patients with pseudophakia were enrolled this study. In the IVTA group, AFI of pseudophakic eyes was significantly decreased at days 1 (p = 0.0487), 7 (p = 0.0201), and 30 (p = 0.0211). In the IVA group, AFI of phakic eyes was transiently increased at day 1 (p = 0.0078) and returned to baseline at day 7, whereas no significant change was observed in AFI of pseudophakic eyes. In the IVR group, there was no significant change in AFI regardless of phakic condition. All groups showed significant reduction in CRT at day 7 and later. CONCLUSION: DME improved after treatment by IVTA, IVR, or IVA, whereas AFI was reduced only in eyes treated with IVTA. The temporal profiles of AFI are likely related to differences in the pharmacological properties of the drugs.

The effect of triamcinolone acetonide or bevacizumab on the levels of proinflammatory cytokines after retinal laser photocoagulation in pigmented rabbits.

Although laser photocoagulation is a gold standard for the treatment of retinal ischemic diseases, thermal burn induces the inflammation and the progression of macular edema. To prevent this complication, combination therapy using anti-vascular endothelial growth factor (VEGF) drugs or steroids is clinically utilized, however the mechanisms are still unclear. In this study, we aimed to evaluate the changes in inflammatory and angiogenic cytokine levels in aqueous humor and vitreous body after intravitreal injection of bevacizumab (IVB) or triamcinolone (IVTA), as well as sub-Tenon injection of triamcinolone (STTA) after retinal laser photocoagulation in rabbits. Pigmented rabbits were treated with retinal laser photocoagulation and divided into 4 groups, namely Control (no additional treatment), IVB, IVTA or STTA accordingly. Samples of vitreous and aqueous humor were collected on post-treatment days 0, 1, 7 and 14. The levels of intraocular VEGF, interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) were measured using an immunoassay. The levels of VEGF, IL-6, ICAM-1 and MCP-1 were significantly elevated 1 day after laser treatment. IVTA and STTA significantly reduced the increase in the levels of VEGF, IL-6, ICAM-1 and MCP-1, while IVB reduced that of VEGF only in aqueous humor and vitreous body. The protein amount in the aqueous humor transiently increased 1 day after laser, and was significantly prevented by IVTA or STTA but not IVB. Data showed that bevacizumab only reduced intraocular VEGF after laser, while triamcinolone suppressed both the expression of VEGF and proinflammatory cytokines. We propose that these cytokine profiles may play an important role in the pathogenesis of inflammation after photocoagulation and the underlying mechanism of treatment with anti-VEGF drug and steroids.

Transcriptional regulation of human ferredoxin reductase through an intronic enhancer in steroidogenic cells.

Ferredoxin reductase (FDXR, also known as adrenodoxin reductase) is a mitochondrial flavoprotein that transfers electrons from NADPH to mitochondrial cytochrome P450 enzymes, mediating the function of an iron-sulfur cluster protein, ferredoxin. FDXR functions in various metabolic processes including steroidogenesis. It is well known that multiple steroidogenic enzymes are regulated by a transcription factor steroidogenic factor-1 (SF-1, also known as Ad4BP). Previously, we have shown that SF-1 transduction causes human mesenchymal stem cell differentiation into steroidogenic cells. Genome-wide analysis of differentiated cells, using a combination of DNA microarray and promoter tiling array analyses, showed that FDXR is a novel SF-1 target gene. In this study, the transcriptional regulatory mechanism of FDXR was examined in steroidogenic cells. A chromatin immunoprecipitation assay revealed that a novel SF-1 binding region was located within intron 2 of the human FDXR gene. Luciferase reporter assays showed that FDXR transcription was activated through the novel SF-1 binding site within intron 2. Endogenous SF-1 knockdown in human adrenocortical H295R and KGN cells decreased FDXR expression. In H295R cells, strong binding of two histone markers of active enhancers, histones H3K27ac and H3K4me2, were detected near the SF-1 binding site within intron 2. Furthermore, the binding of these histone markers was decreased concurrent with SF-1 knockdown in H295R cells. These results indicated that abundant FDXR expression in these steroidogenic cells was maintained through SF-1 binding to the intronic enhancer of the FDXR gene.

Sex-determining region Y-box 2 and GA-binding proteins regulate the transcription of liver receptor homolog-1 in early embryonic cells.

Pluripotent stem cells maintain their pluripotency and undifferentiated status through a network of transcription factors. Liver receptor homolog-1 (Lrh-1) is one of these, and regulates the expression of other important transcription factors such as Oct-3/4 and Nanog. In early embryo and embryonic stem (ES) cells, Lrh-1 is transcribed using a unique promoter. In this study, we investigated the transcriptional regulation of embryonic Lrh-1 using ES and embryonal carcinoma F9 cells. Reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays demonstrated that Sox2 and Gabp proteins bind to the promoter region of embryonic Lrh-1, and are necessary for its activation. The Sox2 site showed strong promoter activity and affinity for protein binding. Upon differentiation into the parietal endoderm by retinoic acid and cAMP, Lrh-1 promoter activity and transcripts were markedly reduced within 24 h. At the same time, Sox2 and Gabp binding to the promoter region of Lrh-1 were decreased, followed by a reduction of their expression. These results indicate that embryonic Lrh-1 expression is regulated by both Sox2 and Gabp. Our study presents new insights into the transcription factor network of pluripotent stem cells.

Determinants of anterior chamber angle narrowing after mydriasis in the patients with cataract.

PURPOSE: To identify the determinants of anterior chamber angle narrowing after mydriasis by quantitative assessment of the anterior chamber components using anterior segment optical coherence tomography (AS-OCT). METHODS: In this intervention study, anterior chamber angle analysis was performed using AS-OCT in patients with cataract before pharmacological pupillary dilation and 30 min afterwards. Angle narrowing was quantified by the change of angle opening distance 500 after mydriasis (ΔAOD500). Multivariate linear regression and stepwise selection regression were used to identify which parameters in AS-OCT significantly determined ΔAOD500. RESULTS: One hundred and two Japanese patients (age, mean ± standard deviation, 71.9 ± 11.2 years) were enrolled. Multivariate analysis indicated that smaller ΔAOD500 were significantly associated with larger lens vault (LV; P < 0.001), larger iris area (IA; P = 0.003), and posterior corneal arch distance (PCAL; P = 0.01). Stepwise linear regression analysis revealed that smaller ΔAOD500 was independently associated with larger LV (partial R (2) = 0.232, P < 0.001), larger IA (partial R (2) = 0.080, P = 0.001), and smaller PCAL (partial R (2) = 0.066, P = 0.002) before mydriasis. These three factors explained 37.7 % of the decrease in ΔAOD500. CONCLUSION: Larger LV, larger IA, and smaller PCAL contribute considerably to anterior chamber angle narrowing after mydriasis in patients with cataract.

C/EBPß (CCAAT/enhancer-binding protein ß) mediates progesterone production through transcriptional regulation in co-operation with SF-1 (steroidogenic factor-1).

The transcription factor SF-1 (steroidogenic factor-1) is a master regulator of steroidogenesis. Previously, we have found that SF-1 induces the differentiation of mesenchymal stem cells into steroidogenic cells. To elucidate the molecular mechanisms of SF-1-mediated functions, we attempted to identify protein components of the SF-1 nuclear protein complex in differentiated cells. SF-1 immunoaffinity chromatography followed by MS/MS analysis was performed, and 24 proteins were identified. Among these proteins, we focused on C/EBPß (CCAAT/enhancer-binding protein ß), which is an essential transcription factor for ovulation and luteinization, as the transcriptional mechanisms of C/EBPß working together with SF-1 are poorly understood. C/EBPß knockdown attenuated cAMP-induced progesterone production in granulosa tumour-derived KGN cells by altering STAR (steroidogenic acute regulatory protein), CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and HSD3B2 (hydroxy-δ-5-steroid dehydrogenase, 3ß- and steroid δ-isomerase 2) expression. EMSA and ChIP assays revealed novel C/EBPß-binding sites in the upstream regions of the HSD3B2 and CYP11A1 genes. These interactions were enhanced by cAMP stimulation. Luciferase assays showed that C/EBPß-responsive regions were found in each promoter and C/EBPß is involved in the cAMP-induced transcriptional activity of these genes together with SF-1. These results indicate that C/EBPß is an important mediator of progesterone production by working together with SF-1, especially under tropic hormone-stimulated conditions.

Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis.

Steroidogenic factor 1 (SF-1) is a master regulator for steroidogenesis. In this study, we identified novel SF-1 target genes using a genome-wide promoter tiling array and a DNA microarray. SF-1 was found to regulate human glutathione S-transferase A (GSTA) family genes (hGSTA1-hGSTA4), a superfamily of detoxification enzymes clustered on chromosome 6p12. All hGSTA genes were up-regulated by transduction of SF-1 into human mesenchymal stem cells, while knockdown of endogenous SF-1 in H295R cells down-regulated all hGSTA genes. Chromatin immunoprecipitation assays, however, revealed that SF-1 bound directly to the promoters of hGSTA3 and weakly of hGSTA4. Chromosome conformation capture assays revealed that the coordinated expression of the genes was based on changes in higher-order chromatin structure triggered by SF-1, which enables the formation of long-range interactions, at least between hGSTA1 and hGSTA3 gene promoters. In steroidogenesis, dehydrogenation of the 3-hydroxy group and subsequent Δ(5)-Δ(4) isomerization are thought to be enzymatic properties of 3ß-hydroxysteroid dehydrogenase (3ß-HSD). Here, we demonstrated that, in steroidogenic cells, the hGSTA1 and hGSTA3 gene products catalyze Δ(5)-Δ(4) isomerization in a coordinated fashion with 3ß-HSD II to produce progesterone or Δ(4)-androstenedione from their Δ(5)-precursors. Thus, hGSTA1 and hGSTA3 gene products are new members of steroidogenesis working as Δ(5)-Δ(4) isomerases.

Aldose reductase inhibitor counteracts the enhanced expression of matrix metalloproteinase-10 and improves corneal wound healing in galactose-fed rats.

PURPOSE: We investigated the effect of an aldose reductase inhibitor (ARI) and the role of matrix metalloproteinase (MMP)-10 on recovery after corneal epithelium removal in a rat diabetic keratopathy model. METHODS: Three-week-old Sprague-Dawley rats were fed the following diets for 6 weeks: normal MF chow (MF), 50% galactose (Gal), and 50% Gal containing 0.01% ARI (Gal +ARI). The corneal epithelium was removed using n-heptanol, and the area of epithelial defects was photographed and measured every 24 h. Real-time reverse transcriptase PCR, western blotting, and immunohistochemistry were used to determine the expression profile of MMP-10 and integrin α3. RESULTS: Compared to the MF control group, the amount of galactitol in the Gal group increased approximately 200-fold, which was reduced to sevenfold by ARI treatment. The area of corneal erosion in the Gal group was significantly larger than in the MF group at 72 h and thereafter (p<0.01, unpaired t test). The expression level of MMP-10 was enhanced at both the protein and mRNA levels by exposure to a high concentration of Gal, while integrin α3 expression decreased at the protein level but remained unchanged at the mRNA level. Delayed epithelial wound healing and alterations in the expression levels of MMP-10 and integrin α3 were normalized by ARI. The corneal erosion closure rate was significantly decreased with topical recombinant MMP-10. CONCLUSIONS: These studies confirm that the increased expression of MMP-10 induced by Gal feeding is counteracted by ARI treatment and suggest a role of MMP-10 in modulating corneal epithelial wound healing.

Turnover of Microaneurysms After Intravitreal Injections of Faricimab for Diabetic Macular Edema.

Purpose: Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME. Methods: We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography. Results: We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment. Conclusions: In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.

Changes in corneal higher-order aberrations during treatment for infectious keratitis.

This study aimed to quantify the changes in corneal higher-order aberrations (HOAs) before and after treatment for infectious keratitis and verify the correlation between corneal HOAs and visual acuity. Corneal HOAs were analysed using swept-source anterior segment optical coherence tomography (AS-OCT). Ninety-eight eyes of 96 consecutive patients with infectious keratitis treated with topical eye drops were retrospectively evaluated. Corneal HOAs increased with the infection but decreased with infection resolution following antimicrobial treatment. Corneal HOAs became larger as the degree of corneal findings became more severe. The increase in HOAs of the total cornea was correlated with the decrease in visual acuity both before and after treatment (4 mm, ρ = 0.530 and 0.590; 6 mm, ρ = 0.479 and 0.567, respectively; all P < 0.0001). Furthermore, pretreatment HOA (anterior, 6 mm), pretreatment logMAR best spectacle-corrected visual acuity, and age were prognostic factors significantly associated with posttreatment visual acuity (ß = 0.31, P = 0.013; ß = 0.36, P < 0.0001; and ß = 0.35, P = 0.0007, respectively) (adjusted R2 = 0.474). These results indicate that corneal HOAs quantified using AS-OCT can be used as an objective index to evaluate corneal optical function during the treatment of infectious keratitis.

Chronic Antioxidant Capacity Loss in Anterior Chamber Environment After Iridectomy.

Purpose: To compare the ascorbic acid concentration and total antioxidant capacity in the aqueous humor of pigmented Rex rabbits after sham operation (control), iridectomy, and trabeculectomy. Methods: Pigmented Rex rabbits were divided into control, iridectomy, and trabeculectomy groups and followed up for 12 months after surgery. Ascorbic acid concentration and total antioxidant capacity in the aqueous humor, intraocular pressure, and the occurrence of cataracts were examined in each group. Results: The ascorbic acid concentration and total antioxidant capacity after iridectomy and trabeculectomy were significantly lower at one week and at one, six, and 12 months after operation than those in the control group (P ≤ 0.03). Ascorbic acid concentration was positively and significantly correlated with total antioxidant capacity in the aqueous humor (P < 0.01). Compared to the control and the iridectomy groups, intraocular pressure in the trabeculectomy group was significantly lower at one week and at one and six months after surgery (one week: P < 0.01 and P < 0.01, respectively; one month: P < 0.01 and P = 0.03, respectively; six months: P = 0.03). Histological findings in the iridectomy and trabeculectomy groups included the appearance of vacuoles in the lens at six and 12 months after surgery. Conclusions: Iridectomy causes a sustained decrease in ascorbic acid concentration, followed by a long-term decrease in the total antioxidant capacity within the aqueous humor. Translational Relevance: The animal model possibly predicts the vulnerability focusing on the antioxidant level in the anterior chamber environment after trabeculectomy and iridectomy per se in clinical settings.

Glycemic Control after Initiation of Anti-VEGF Treatment for Diabetic Macular Edema.

Diabetic macular edema (DME) induces visual disturbance, and intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs are the accepted first-line treatment. We investigate its impact on glycemic control after starting VEGF treatment for DME on the basis of a questionnaire and changes in hemoglobin A1c (HbA1c). We conducted a retrospective multicenter study analyzing 112 patients with DME who underwent anti-VEGF therapy and their changes in HbA1c over two years. Central retinal thickness and visual acuity significantly improved at three months and throughout the period after initiating therapy (p < 0.0001); a significant change in HbA1c was not found. A total of 59.8% of patients became more active in glycemic control through exercise and diet therapy after initiating therapy, resulting in a significantly lower HbA1c at 6 (p = 0.0047), 12 (p = 0.0003), and 18 (p = 0.0117) months compared to patients who did not. HbA1c was significantly lower after 18 months in patients who stated that anti-VEGF drugs were expensive (p = 0.0354). The initiation of anti-VEGF therapy for DME affects HbA1c levels in relation to more aggressive glycemic control.

Long-Term Outcome After Superficial Keratectomy of the Abnormal Epithelium for Partial Limbal Stem Cell Deficiency.

PURPOSE: To investigate the etiology and long-term surgical prognosis of the abnormal epithelium for partial limbal stem cell deficiency (LSCD), following superficial keratectomy DESIGN: Retrospective, interventional case series METHODS: This single-center, retrospective study was conducted to assess the prognosis of consecutive patients who underwent superficial keratectomy, with or without amniotic membrane transplantation (AMT), for the treatment of partial LSCD, from 2010 to 2019. We analyzed the etiologies of partial LSCD, surgical success rate, prognosis for recurrent cases, and the improvement in visual acuity. RESULTS: We included 40 patients (51 eyes) with partial LSCD. All eyes were in clinical stage II without dense fibrovascular tissue. Idiopathy was the most common etiology (39%), followed by multiple surgeries involving the corneoscleral limbus (19%). All eyes attained corneal reepithelialization and transparency. Furthermore, the visual acuity improved or remained unchanged postoperatively. We observed recurrence in 19 eyes (37%) with a mean follow-up period of 26.3 months. Despite no significant difference in the recurrence rates among different etiologies, postoperative delayed epithelialization and extensive limbal involvement were identified as risk factors for recurrence (P < .001 and P = .013, respectively). Repeat surgeries were performed in 16 eyes. The final success rate was 84%. CONCLUSIONS: Superficial keratectomy is useful for the treatment of partial LSCD of varied etiologies, with an expected improvement in visual acuity postoperatively. Although the procedure can be repeated and have a high success rate, there have been several cases of recurrence in the long-term postoperative course.

Topical bromfenac reduces multiple inflammatory cytokines in the aqueous humour of pseudophakic patients.

Intraocular surgery is associated with increased ocular inflammation. If maintained for a prolonged period after surgery, this inflammation can cause various complications, including subconjunctival fibrosis and bleb scarring. This clinical trial was a prospective, randomised, single-blind, interventional study comparing the efficacy and safety of 0.1% bromfenac sodium ophthalmic solution and 0.02% fluorometholone ophthalmic suspension in the inhibition of multiple inflammatory cytokines in the aqueous humour of 26 patients with pseudophakic eyes who had undergone phacoemulsification and intraocular lens implantation. The patients were randomly assigned to one of the trial drugs, and aqueous humour samples were collected before and after drug administration. Platelet-derived growth factor-AA levels significantly decreased in both drug groups, but they were significantly higher in the fluorometholone group than in the bromfenac group (P = 0.034). Bromfenac also significantly decreased vascular endothelial growth factor level (P = 0.0077), as well as monocyte chemoattractant protein-1 level (P = 0.013), which was elevated for a prolonged period after phacoemulsification. These data suggest that bromfenac is useful to alleviate prolonged microenvironmental alterations in the aqueous humour of pseudophakic eyes.

Microaneurysm density in residual oedema after anti-vascular endothelial growth factor therapy for diabetic macular oedema.

PURPOSE: To investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti-vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO). METHODS: Patients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography. RESULTS: We examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029). CONCLUSION: High MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab.

Aqueous Cytokine Levels Are Associated With Progression of Peripheral Anterior Synechiae After Descemet Stripping Automated Endothelial Keratoplasty.

Purpose: To evaluate the association between total protein and cytokine levels in aqueous humor (AqH) and the progression of peripheral anterior synechiae (PAS) after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: This prospective study included 146 consecutive patients who underwent DSAEK. Preoperative levels of total protein and 20 cytokines in AqH were measured. Using three-dimensional anterior segment optical coherence tomography, we assessed the iridotrabecular contact (ITC) area before and at 3, 6, and 12 months after DSAEK. Correlations between the total protein and cytokine levels in the AqH and ITC area were analyzed. Results: ITC was observed in 47 eyes (32.2%) after DSAEK. The ITC area increased from 2.00 ± 4.42 mm2 preoperatively to 3.00 ± 6.85 mm2 at 12 months. The total protein level in AqH was significantly higher in eyes with ITC progression than in those without (1.45 ± 1.03 mg/mL vs. 1.00 ± 0.57; P = 0.04) and was significantly positively correlated with the progression of ITC area after DSAEK (at 6 months, r = 0.311 and P = 0.005; at 12 months, r = 0.342 and P = 0.0004). The ITC area at 12 months was significantly correlated with the preoperative AqH levels of interleukin-8 (r = 0.252; P = 0.021), interferon-γ (r = 0.318; P = 0.009), and soluble intercellular adhesion molecule-1 (r = 0.292; P = 0.004). Multivariate analyses showed that the total protein levels in AqH and the presence of preoperative ITC were significant risk factors for increased ITC area after DSAEK (ß = 0.193-0.574; all P < 0.02). Conclusions: Higher preoperative total protein and specific cytokine levels in AqH were associated with ITC formation after DSAEK. Translational Relevance: Our findings indicate that chronic pathological changes in AqH can cause PAS progression and glaucoma after DSAEK.